Aerosolized nanoparticulates, found both in the environment and occupational settings, are readily inhaled and can travel to the distal airways and alveolar spaces while avoiding most of the pulmonary defense and entrapment mechanisms. Carbon nanotubes, a relatively new nanoparticulate which has seen a marked increase in production due to multiple potential biomedical and electrical commercial uses, has shown significant cytotoxicity and genotoxocity towards multiple cell lines in culture and can induce pulmonary fibrosis and inflammation in mouse models as well as systemic immune suppression. In particular, carbon nanotubes and other nanoparticulates have been shown to inhibit phagocytosis by macrophages. However, no work has been performed to explore the consequences of nanotube induced immune suppression in models when challenged with a pulmonary infection. Our laboratory investigates the host/pathogen interaction using Pseudomonas aeuruginosa, an environmental and nosocomial pathogen which has been linked to severe pulmonary infections in individuals with cystic fibrosis, chronic obstructive pulmonary disease, immunocompromised patients, and the elderly. The overarching goal of my project is to examine the impact that exposure to carbon nanotubes has on the host in response to infection by P. aeuruginosa and determine the underlying mechanisms to explain observed changes. In this proposal, I will investigate the pulmonary immune response to infection by P. aeuruginosa following chronic exposure to helical carbon nanotubes (HCNT) by focusing on the macrophage function. Early work in our lab has demonstrated impaired phagocytosis of P. aeuruginosa by RAW 264.7 macrophages following exposure to HCNTs as well as an enhanced acute inflammatory response to P. aeuruginosa infection in mice. Interestingly, clearance of P. aeuruginosa in mice was not affected by prior treatment with HCNTs, suggesting that phagocytosis by alveolar macrophages plays a minor role in the acute immune response. This proposal seeks to confirm this finding. Additionally, we will be exploring whether HCNTs impair surfactant protein A (SP-A) mediated phagocytosis in our models as it has been shown that nanotubes will absorb proteins, including the surfactant proteins, onto their surface. Finally, we will be using a chronic P. aeuruginosa infection model to examine the impact of HCNT exposure as it relates to pulmonary inflammation, fibrosis, and clearance.